Artikel
The MRZ reaction and specific autoantibody formation assist in the distinction between ANA-positive multiple sclerosis and rheumatic diseases with cerebral involvement
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Veröffentlicht: | 5. Februar 2019 |
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Gliederung
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Background: Rheumatic diseases with involvement of the central nervous system (RDwCNS) may mimic multiple sclerosis (MS), inversely, up to 60% of MS patients have antinuclear autoantibodies (ANAs) and may be misdiagnosed as RDwCNS. A positive MRZ-reaction (MRZR), which is composed of three antibody indices (AI) against measles, rubella, and varicella zoster virus, determined in paired samples from serum and cerebrospinal fluid (CSF) is frequently positive in MS. Goal of this study was to investigate, whether MRZR and testing for extractable nuclear antigens (ENA) is useful to distinguish RDwCNS from ANA-positive MS.
Methods: MRZR was evaluated in 40 patients with RDwCNS and compared to 68 ANA-positive MS patients. An AI result ≥1.5 was indicative for intrathecal IgG-production against the respective pathogen. Two stringency levels, MRZR-1 and MRZR-2 (≥1/3 AIs respectively ≥2/3 positive) were applied. Autoantibody diagnostics included ANA, ENA (+DFS70), antiphospholipid-antibodies (APA), and antineutrophil cytoplasmic antibodies (ANCA). CNS involvement of RDwCNS was defined as clinical manifestation with neurological symptoms and signs of inflammation in CSF-analysis and/or cerebral/spinal magnetic resonance imaging (MRI).
Results: Within the RDwCNS-group, 32 patients (80%) suffered from systemic lupus erythematosus, eight had a small vessel vasculitis. In both groups >70% were female. There was no statistical difference between the two groups regarding age and sex. All MS patients were ANA-positive in indirect immunofluorescence. ENA and APA were found more frequently in RDwCNS (p<0.0001). No presence of DFS70-antibodies was detected in the RDwCNS-group, but in 2.9% of the MS-patients. Only 20% of RDwCNS-patients had a positive MRZR-1 compared to 80.9% within the MS-group (p<0.0001). The more specific MRZR-2 was positive in 60% of the MS patients compared to only 8.5% of the RDwCNS-patients (p<0.0001). By using a higher threshold for a positive AI (>2.0), the prevalence of positive MRZR-2 dropped to 2.5% (n=1) in RDwCNS compared to 36.8% (n=25) in MS-patients (p<0.0001). Oligoclonal bands were found in 89.7% of the MS and 32.6% of the RDwCNS-patients (p<0.0001). In absence of specific autoantibodies a positive MRZR separates RDwCNS from MS with a specificity of 97.5%.
Conclusion: Considering the high specificity we suggest combining MRZR and autoantibody diagnostics to differentiate RDwCNS from MS.